Pruritus related to trastuzumab and pertuzumab in HER2 + breast cancer patients.

PURPOSE: The combination of trastuzumab and pertuzumab (HP) as part of a taxane-based regimen has shown benefit in the adjuvant and metastatic HER2 + breast cancer setting. In the CLEOPATRA trial, pruritus was reported in 11-17.6% of patients. The clinical phenotype and potential treatment strategies for this event have not been reported. METHODS: A retrospective review of 2583 patients receiving trastuzumab and pertuzumab for the treatment of HER2 + breast cancer from 11/23/2011 to 6/21/2021 was performed at Memorial Sloan Kettering Cancer Center (MSKCC). Patient demographics, pruritus characteristics, and treatments as documented in the electronic medical record (EMR) were included in this analysis. RESULTS: Of 2583 pts treated with HP, 122 (4.72%) with pruritus were identified. On average, patients experienced pruritus 319.0 days (8-3171) after initiation of HP. The upper extremities (67.4%), back (29.3%), lower extremities (17.4%), and shoulders (14.1%) were the most commonly affected regions. Grade 1/2 pruritus (97.6%) occurred in most cases. Patients responded primarily to treatment with topical steroids (52.2%), antihistamines (29.9%), emollients (20.9%), and gabapentinoids (16.4%). Of those with pruritus, 4 patients (3.3%) required treatment interruption or discontinuation. CONCLUSIONS: Pruritus is uncommon in patients on trastuzumab and pertuzumab, generally a chronic condition, with gabapentinoids or antihistamines representing effective therapies.

Demographic and clinical characteristics of acute myeloid leukaemia diagnosed and treated at the tertiary level in Afghanistan.

A retrospective case series design was conducted to elucidate the demographic features of acute myeloid leukaemia in Afghanistan. This study was conducted at Jamhuriat Hospital and French Medical Institute for Mothers and Children, Kabul, Afghanistan. A total of 203 patients with AML diagnosed and managed at Jamhuriat Hospital from 1 March 2018 to 31 March 2020, were included in the current study. The median age at diagnosis was 27 years. Housewives represented the largest subset of patients from an occupational point of view constituting 37.44% of the total sample population and 81.72% of the female population, followed by 20.69% patients who were students of which 14.77% were male and 5.91% were female, and 17.24% were farmers, which constituted 31.81% of the male population. Similarly, 69.95% of individuals presented with infection, 57.14% presented with bone tenderness, 46.3% presented with bleeding tendencies, 55.66% had hepatomegaly and/or splenomegaly, and 27.58% of patients had lymphadenopathy. Considering the chemotherapeutic regime, 64.53% of the individuals received standard 7 + 3 (cytarabine + daunorubicin) induction regimen, 10.68% of those received 5 + 2 re-induction chemotherapy (cytarabine + daunorubicin). 10.84% who were diagnosed with acute promyelocytic leukaemia received all-trans-retinoic acid + arsenic trioxide, while 5.42% of patients defaulted chemotherapy. High prevalence was noted in young individuals. Similarly, a high proportion of patients were constituted by housewives.

Efficacy of immunotherapy with combination of cryotherapy and topical imiquimod for treatment of Kaposi sarcoma.

Multiple treatment modalities for Kaposi sarcoma (KS) have been reported, including chemotherapy, radiation therapy, surgical excision, electrochemotherapy, and cryotherapy. Common topical treatments include timolol, imiquimod, and alitretinoin. We searched our institutional database for patients with ICD-9 or 10 codes for KS seen by a dermatologist with experience in KS management from July 1, 2004 to January 1, 2022. We screened patient charts to include patients who received combination therapy of cryotherapy followed by topical imiquimod three times a week for 2 months (n = 9). Patients were followed in the clinic every 3 months. Time to resolution was assessed by photographic evidence of resolution as determined by a dermatologist and corroborated with clinical documentation in patient charts. Median age (IQR) at KS diagnosis was 58 (27.5) years. All patients were male (n = 9, 100%). Majority were white (n = 7, 78%) and non-Hispanic (n = 8, 89%). Five (56%) had classic KS, one (11%) had HIV-associated KS, and three (33%) were HIV-negative men who have sex with men. Median time to resolution was 30.5 weeks, with a median of two treatments. In our study, 93% (n = 42/45) of lesions and 89% (n = 8/9) of patients experienced complete resolution during a median (range) duration of follow-up of 58 (13-209) weeks. Side effects were limited to pain during cryotherapy, occasional blister formation after cryotherapy, and mild inflammation due to imiquimod. No infections were observed. Combination therapy of cryotherapy and topical imiquimod may be an efficacious and comparatively low-risk treatment for limited, cutaneous KS.

A phase 2 biomarker-driven study of ruxolitinib demonstrates effectiveness of JAK/STAT targeting in T-cell lymphomas.

Signaling through JAK1 and/or JAK2 is common among tumor and nontumor cells within peripheral T-cell lymphoma (PTCL). No oral therapies are approved for PTCL, and better treatments for relapsed/refractory disease are urgently needed. We conducted a phase 2 study of the JAK1/2 inhibitor ruxolitinib for patients with relapsed/refractory PTCL (n = 45) or mycosis fungoides (MF) (n = 7). Patients enrolled onto 1 of 3 biomarker-defined cohorts: (1) activating JAK and/or STAT mutations, (2) ≥30% pSTAT3 expression among tumor cells by immunohistochemistry, or (3) neither or insufficient tissue to assess. Patients received ruxolitinib 20 mg PO twice daily until progression and were assessed for response after cycles 2 and 5 and every 3 cycles thereafter. The primary endpoint was clinical benefit rate (CBR), defined as the combination of complete response, partial response (PR), and stable disease lasting at least 6 months. Only 1 of 7 patients with MF had CBR (ongoing PR > 18 months). CBR among the PTCL cases (n = 45) in cohorts 1, 2, and 3 were 53%, 45%, and 13% (cohorts 1 & 2 vs 3, P = .02), respectively. Eight patients had CBR > 12 months (5 ongoing), including 4 of 5 patients with T-cell large granular lymphocytic leukemia. In an exploratory analysis using multiplex immunofluorescence, expression of phosphorylated S6, a marker of PI3 kinase or mitogen-activated protein kinase activation, in <25% of tumor cells was associated with response to ruxolitinib (P = .05). Our findings indicate that ruxolitinib is active across various PTCL subtypes and support a precision therapy approach to JAK/STAT inhibition in patients with PTCL. This trial was registered at www.clincialtrials.gov as #NCT02974647.

Risk factors associated with esophageal cancers, diagnosed at tertiary level in Afghanistan: a descriptive cross-sectional study.

BACKGROUND: Worldwide, esophageal cancer (EC) is a common cancer in term of incidence and mortality and is the 4th common cancer in Afghanistan. Current study aimed to evaluate the profile of risk factors for EC among patients diagnosed at tertiary level in Afghanistan. METHODOLOGY: A descriptive cross-sectional study was carried out between January 2019 up to February 2021 including all esophageal cancers diagnosed at pathology department of French Medical Institute for Mothers and Children, Afghanistan. RESULT: 240 diagnosed cases were analyzed, in which 59.40% of squamous cell carcinoma and 41.07% Adenocarcinoma. Both histopathological type of were predominantly diagnosed in males. The majority of the patients were residents of rural areas. More than 80% of the patients were illiterate with only less than 2% completing higher education. Majority of the patients were laborers and farmers while less than 10% were employed. According to income assessment, more than 80% were from low-income household, the rest from middle-income and none from high-income family. Oral snuff consumption was noted in 33.9% of squamous cell carcinoma patients and 40% adenocarcinoma patients whereas, family history of esophageal cancer was observed in 37.8% and 36.7% in both types of carcinomas, respectively. More than 60% of both types of carcinomas patients were hot tea drinkers. CONCLUSION: Current study demonstrated that most patients diagnosed with esophageal cancers were male, uneducated, belongs to low-income groups, lives in rural areas. These findings suggest distribution of esophageal cancer in specific socioeconomic groups, clearly demonstrating the need further analytical study.

Primary cutaneous T-cell lymphomas other than mycosis fungoides and Sézary syndrome. Part II: Prognosis and management.

Primary cutaneous T-cell lymphomas (CTCLs) other than mycosis fungoides (MF) and Sézary syndrome (SS) encompass a heterogenous group of non-Hodgkin lymphomas with variable clinical courses, prognoses, and management approaches. Given the morphologic and histologic overlap among the CTCL subtypes and other T-cell lymphomas with cutaneous manifestations, thorough evaluation with clinicopathologic correlation and exclusion of systemic involvement are essential prior to initiating therapy. Staging and treatment recommendations vary, depending on the subtype, clinical behavior, and treatment response. Generally, for subtypes in which staging is recommended, Ann Arbor or tumor, node, metastasis staging specific to CTCL other than MF or SS are used. For many subtypes, there is no standard treatment to date. Available recommended treatments range widely, from no active or minimal intervention with skin-directed therapy to aggressive systemic therapies that include multi-agent chemotherapy with consideration for hematopoietic stem cell transplant. Emerging targeted therapies, such as brentuximab, a chimeric antibody targeting CD30, show promise in altering the disease course of non-MF/SS CTCLs.

Primary cutaneous T-cell lymphomas other than mycosis fungoides and Sézary syndrome. Part I: Clinical and histologic features and diagnosis.

Primary cutaneous T-cell lymphomas (CTCLs) are defined as lymphomas with a T-cell phenotype that present in the skin without evidence of systemic or extracutaneous disease at initial presentation. CTCLs other than mycosis fungoides and Sézary syndrome (SS) account for approximately one third of CTCLs and encompass a heterogenous group of non-Hodgkin lymphomas, ranging from indolent lymphoproliferative disorders to aggressive malignancies with a poor prognosis. The spectrum of CTCLs continues to broaden as new provisional entities are classified. Given the morphologic and histologic overlap among CTCLs and other diagnoses, a thorough clinical history, physical evaluation, and clinicopathologic correlation are essential in the work up and diagnosis of these rare entities. This article will summarize the epidemiologic, clinical, pathologic, and diagnostic features of CTCLs other than mycosis fungoides and SS.

Dermatologic infections in cancer patients treated with checkpoint inhibitors.

BACKGROUND: The incidence of dermatologic infections in patients receiving checkpoint inhibitors (CPIs) has not been systematically described. OBJECTIVE: Identify the incidence of dermatologic infections in patients who received CPIs. METHODS: Retrospective review of dermatologic infections in patients who received CPIs between 2005 and 2020 and were evaluated by dermatologists at Memorial Sloan Kettering Cancer Center. RESULTS: Of 2061 patients in the study, 1292 were actively receiving CPIs (≤ 90 days since the last dose) and 769 had previously been on CPIs (> 90 days since the last dose). The dermatologic infection rate was significantly higher in patients with active CPI treatment (17.5%) than in patients not actively being treated (8.2%; P < .0001). In patients on CPIs, 82 (36.2%), 78 (34.5%), and 48 (21.2%) had bacterial, fungal, and viral infections, respectively, and 18 (8.0%) had polymicrobial infections. Anti-cytotoxic T-lymphocyte-associated antigen-4 monotherapy was associated with the highest risk of infection (hazard ratio, 2.93; 95% confidence interval, 1.87 to 4.60; P < .001). LIMITATIONS: Retrospective design and sample limited to patients referred to dermatology. CONCLUSIONS: Patients actively receiving CPIs are more susceptible to dermatologic infections, with anti-cytotoxic T-lymphocyte-associated antigen-4 monotherapy carrying the highest risk, suggesting that the index of suspicion for infections should be increased in these patients to minimize morbidity and optimize care.

Cutaneous Manifestations of EGFR-Inhibitors in African Americans and Treatment Considerations.

Epidermal growth factor (EGFR)-inhibitors have emerged as the primary therapy in advanced solid tumor malignancies because of improvement in survival with overall favorable side effect profile. However, 50–90% of patients treated with EGFR-inhibitors develop a follicular or acneiform rash, which can be symptomatic and source of psychosocial distress, negatively impacting quality of life. As this acneiform rash is a well-recognized cutaneous toxicity of EGFR-inhibitors, a treatment algorithm has been proposed for management based on severity. However, treatment options for EGFR-inhibitor induced rash may not be generalizable to African Americans whose differences in skin biology and sensitivity present pathophysiologic challenges. Herein, we present a case of an African American patient who developed this acneiform rash while on cetuximab. We also review the few cases that have been reported in the literature of EGFR-inhibitor rash in African Americans, highlighting important management considerations in this patient population. J Drugs Dermatol. 2020;19(9):894-896. doi:10.36849/JDD.2020.5275.

Clinical Characteristics and Disease Course in Black Patients With Lymphomatoid Papulosis: A Case Series

INTRODUCTION: Lymphomatoid papulosis (LyP) is a CD30+ T-cell lymphoproliferative disorder (LPD) presenting as a recurrent eruption of papules and nodules which resolve spontaneously. CD30+ LPD prevalence in African American (AA)/Black patients is lower compared to White patients. CD30+ LPD has been recently reported to have worse outcomes in AA patients compared to White patients. METHODS: A retrospective chart review identified eight AA patients with LyP. We describe our experience with these eight patients and review the literature on similar cases. RESULTS: In half of the eight included patients, lesions occurred 1-4 years before they were diagnosed. In six patients (75%), resolution of the lesions resulted in hyperpigmented macules and scars. Five patients (63%) had also mycosis fungoides. Most of the patients who were followed (4/7, 57%) did not have complete resolution at their last visit, despite different treatment approaches. Discussion: Our results highlight that although LyP has an indolent course in AA/Black patients, residual hyperpigmentation and scars frequently occur, highlighting the need for better treatments of this lymphoproliferative disorder in this specific population. J Drugs Dermatol. 2020;19(1):89-91. doi:10.36849/JDD.2020.4602

Primary synovial sarcoma in anal canal: Report of a very rare case.

Extensive studies are required to understand the behavior as well as prognosis of SS in the colorectal region. IHC staining is essential for the accurate diagnosis when a lesion is encountered at an unusual site.

Cutaneous lymphomas in African American/Black patients: pitfalls and presentations.

This review describes and highlights differences in clinical presentations of cutaneous lymphomas (CLs), particularly in darker skin types, i.e., Skin of Color (SOC). We illustrate differences in clinical features on physical exam that can be a diagnostic challenge and suggest ways to recognize and identify these conditions at an early stage through a high level of suspicion. The review includes a summary of the epidemiology of various CLs, specifically highlighting the presentation and incidence in African American/Black patients, where the data are available. We also include a discussion of adult HTLV-1-associated T-cell leukemia/lymphoma (ATLL) which, although a systemic T-cell lymphoma, may present with skin manifestations and mimic MF, other CTCL subtypes, or other inflammatory dermatoses. Finally, this review highlights the possible use of imaging modalities, such as dermoscopy and reflectance-confocal microscopy, in diagnosing and recognizing cutaneous lymphomas in patients with darker skin types.

Pruritus Related to Trastuzumab and Pertuzumab in HER2+ Breast Cancer Patients.

Purpose: The combination of trastuzumab and pertuzumab (HP) as part of a taxane-based regimen has shown benefit in the adjuvant and metastatic HER2+ breast cancer setting. In the CLEOPATRA trial, pruritus was reported in 11-17.6% of patients. The clinical phenotype and potential treatment strategies for this event have not been reported. Methods: A retrospective review of 2583 patients receiving trastuzumab and pertuzumab for the treatment of HER2+ breast cancer from 11/23/2011 to 6/21/2021 was performed at Memorial Sloan Kettering Cancer Center (MSKCC). Patient demographics, pruritus characteristics, and treatments as documented in the electronic medical record (EMR) were included in this analysis. Results: Of 2583 pts treated with HP, 122 (4.72%) with pruritus were identified. On average, patients experienced pruritus 319.0 days (8-3171) after initiation of HP. The upper extremities (67.4%), back (29.3%), lower extremities (17.4%), and shoulders (14.1%) were the most commonly affected regions. Grade 1/2 pruritus (97.6%) occurred in most cases. Patients responded primarily to treatment with topical steroids (52.2%), antihistamines (29.9%), emollients (20.9%), and gabapentinoids (16.4%). Of those with pruritus, 4 patients (3.3%) required treatment interruption or discontinuation. Conclusions: Pruritus is uncommon in patients on trastuzumab and pertuzumab, generally a chronic condition, with gabapentinoids or antihistamines representing effective therapies.

Hypokalemic periodic paralysis in a teenage boy after an intense period of exercise: A rare case report.

Key Clinical Messages: Diagnosis of rare even can be missed due to less familiarity with the disorder.In patients with muscle weakness, infectious causes are prioritized.Electrolyte profile not only identifies the problem, but also prevents unnecessary workup. Abstract: In underdeveloped countries, diagnosis of rare disorders is usually delayed due to less familiarity of the clinicians to such disorders. As a result, infectious and inflammatory causes for an ailment are prioritized as compared to non-infectious etiologies. Hypokalemic periodic paralysis (PP) is a rare disorder, characterized by episodic muscle weakness that can rarely be associated with life-threatening cardiac arrhythmia. A teenage Afghan boy presented to the emergency department with an acute flaccid paralysis, that started 1 h after intense exercise The weakness involved both, the upper and lower extremities. Laboratory investigations, led to the impression of hypokalemic PP, precipitated by intense exercise. Accordingly, intravenous potassium chloride infusion diluted with normal saline led to the complete resolution of paralysis as well as correction of electrocardiographic changes. The list of differential diagnosis for flaccid muscle paralysis is wide, which generally requires a extensive investigations, but in hypokalemic PP, a cardinal electrolytes profile can lead towards early diagnosis. High degree of clinical suspicion with appropriate history taking and physical examination helps with the immediate identification and management of this disorder.

Albright hereditary osteodystrophy: Delay in the diagnosis of a rare disorder due to restricted medical services.

A teenage Afghan girl presented with seizure. Clinical features and laboratory investigations revealed elevated serum parathormone, high phosphate levels with low serum calcium. In third-world countries, diagnosis of rare disorders, such as Albright hereditary osteodystrophy (AHO), can usually be delayed due to scarcity of standard medical and diagnostic services.

Meet the expert: Topical management of vulvar dermatoses.

Vulvar dermatoses are often debilitating chronic skin conditions associated with pain and pruritus. In oncologic patients, cancer treatments can precipitate and exacerbate vulvar dermatoses. Cytotoxic chemotherapy, hormonal therapies, and local pelvic radiation therapy can lead to vulvar symptoms, and cancer treatment-induced vulvar conditions include graft-versus-host-disease and radiation dermatitis. There have also been reports of lichen sclerosus development or exacerbation secondary to hormonal therapy and immune checkpoint inhibitors, attributed to proposed hormonal and immunologic pathogenesis of lichen sclerosus. Early recognition and treatment of these conditions can significantly improve quality of life. In this review, we summarize the clinical features and management characteristics of six types of common vulvar dermatoses that may present in the oncologic patient.

Acute lymphoblastic leukemia with clonal evolution due to delay in chemotherapy: A report of a case.

Clonal evolution in acute leukemias is one of the most important factors that leads to therapeutic failure and disease relapse. Delay in therapeutic intervention is one of the reasons that leads toward clonal evolution. In this report, we present a case of acute lymphoblastic leukemia in which therapeutic delay resulted in clonal evolution that was detected by conventional karyotyping and was responsible for non-responsiveness of the disease to conventional chemotherapy. A 17-year-old boy presented with generalized body aches, rapidly progressive pallor and lethargy. Bone marrow analysis was consistent with the diagnosis of B-cell ALL. Karyotypic analysis revealed 46, XY male karyotype. The patient left the hospital due to financial reasons and after 40 days came back to the hospital. Repeated bone marrow analysis including cytogenetic studies revealed presence of three different clones of blast cells: one clone showed 46, XY with del(9p) and t (11;14), second clone showed 46, XY with del(7q) and del(9p), and the third clone showed 46, XY normal karyotype. The patient did not respond to chemotherapy and died within 1 week of induction chemotherapy (HyperCVAD-A). Timely diagnosis and institution of chemotherapy in acute leukemias patients is the key to prevent clonal evolution and thus resistance of the disease to therapeutic interventions.